Incremental cost burden among patients with severe uncontrolled asthma in the United States

BACKGROUND: The economic burden of severe asthma and severe uncontrolled asthma (SUA) is significant. Updated assessments of health care resource utilization (HCRU) and cost are needed given the increase in treatment options and updates to guidelines in recent years. OBJECTIVE: To describe all-cause and asthma-related HCRU and costs among patients with SUA vs patients with nonsevere asthma in the United States using real-world data. METHODS: MarketScan administrative claims databases were used to select adults with persistent asthma for this retrospective analysis between January 1, 2013, and December 31, 2019. Asthma severity status was defined using the Global Initiative for Asthma step 4/5 criteria (index is the earliest date qualifying patients as severe or randomly assigned for nonsevere patients). Patients with SUA were a subset of the severe cohort meeting the following criteria: those who were hospitalized with asthma as the primary diagnosis or had at least 2 emergency department or outpatient visits with an asthma diagnosis and a steroid burst within 7 days. HCRU, costs (allcause and asthma-related defined as medical claims with an asthma diagnosis and pharmacy claims for asthma treatment), work loss, and indirect costs due to absenteeism and short-term disability (STD) were compared between patients with SUA, severe, and nonsevere asthma. Outcomes were reported during a fixed 12-month post-index period using chi-square and t-tests where appropriate. RESULTS: 533,172 patients with persistent asthma were identified (41.9% [223,610]) severe and 58.1% [309,562] nonsevere). Of the severe patients, 17.6% (39,380) had SUA. The mean (SD) all-cause total health care costs were significantly higher in patients with SUA ($23,353 [$40,817]) and severe asthma ($18,554 [$36,147]) compared with those with nonsevere asthma ($16,177 [$37,897], P < 0.001 vs nonsevere asthma). The results were consistent for asthma-related costs. In addition, although patients with severe asthma made up 41.9% of the total study population, they contributed disproportionately higher costs (60.5%) to the total asthma-related direct costs, with the effect more evident among patients with SUA (7.4% of study population contributed 17.7% of the total asthma-related costs). For the subset of patients with asthma with workplace absenteeism, patients with SUA lost more time from work (259.3 vs 236.2 hours lost, P = 0.002; 7.8 vs 5.3 STD days, P < 0.001), and had higher corresponding indirect costs ($5,944 vs $5,415, P = 0.002 for absenteeism related; $856 vs $582, P < 0.001 for STD related) compared with patients with nonsevere asthma. CONCLUSIONS: Patients with SUA have significantly higher asthma-related economic burden compared with patients with nonsevere asthma and contribute a disproportionally higher percentage of asthma-related costs.


METHODS:
MarketScan administrative claims databases were used to select adults with persistent asthma for this retrospective analysis between January 1, 2013, and December 31, 2019. Asthma severity status was defined using the Global Initiative for Asthma step 4/5 criteria (index is the earliest date qualifying patients as severe or randomly assigned for nonsevere patients). Patients with SUA were a subset of the severe cohort meeting the following criteria: those who were hospitalized with asthma as the primary diagnosis or had at least 2 emergency department or outpatient visits with an asthma diagnosis and a steroid burst within 7 days. HCRU, costs (allcause and asthma-related defined as medical claims with an asthma diagnosis and pharmacy claims for asthma treatment), work loss, and indirect costs due to absenteeism and short-term disability (STD) were compared between patients with SUA, severe, and nonsevere asthma. Outcomes were reported during a fixed 12-month post-index period using chisquare and t-tests where appropriate.  ($16,177 [$37,897], P < 0.001 vs nonsevere asthma). The results were consistent for asthma-related costs. In addition, although patients with severe asthma made up 41.9% of the total study population, they contributed disproportionately higher costs (60.5%) to the total asthma-related direct costs, with the effect more evident among patients with SUA (7.4% of study population contributed 17.7% of the total asthma-related costs). For the subset of patients with asthma with workplace absenteeism, patients with SUA lost more time from work (259.3 vs 236.2 hours lost, P = 0.002; 7.8 vs 5.3 STD days, P < 0.001), and had higher corresponding indirect costs ($5,944 vs $5,415, P = 0.002 for absenteeism related; $856 vs $582, P < 0.001 for STD related) compared with patients with nonsevere asthma.

Plain language summary
Asthma is a prevalent chronic condition with continued high economic burden. People with severe uncontrollable asthma (SUA) have problems controlling their asthma and need specific treatments. This analysis aimed to quantify direct and indirect costs incurred among patients with SUA compared with nonsevere asthma using data from insurance claims. Patients with severe asthma had significantly higher costs compared with patients with nonsevere asthma, and those with SUA experienced the highest economic burden.

Implications for managed care pharmacy
Results from this study indicate that patients with SUA bear a much higher economic burden compared with patients with nonsevere asthma to treat their asthma, accruing significantly higher amounts of health care resource utilization, costs, and time lost from employment. Patients with SUA also contributed a disproportionate percentage of asthma-related costs nationally (~7% of patients contributing ~17% of costs), providing further evidence for the need of therapies to successfully manage disease and reduce the occurrence of costly medical interventions.

Economic burden of severe uncontrolled asthma
Benefits Database, and the MarketScan Health Productivity Management (HPM) Database. The Commercial Claims and Medicare databases contain inpatient (IP), outpatient (OP), and OP prescription drug experience of employees and their dependents, covered under a variety of fee-forservice and managed care health plans, including exclusive provider organizations, preferred provider organizations, point of service, indemnity, and health maintenance organizations, as well as retirees with Medicare supplemental insurance paid for by employers. The HPM database contains workplace absence, short-term disability (STD), long-term disability, and workers' compensation data from a subset of Merative's employer clients who contribute to the Commercial Claims Database.

PATIENT SELECTION AND COHORT ASSIGNMENT
Patients with persistent asthma aged 18 years or older were initially selected into the study and were defined as having at least 1 IP or 2 OP nondiagnostic claims (≥30 days apart) with a diagnosis code of asthma between January 1, 2013, and December 31, 2019. Persistent disease was defined by the Healthcare Effectiveness Data and Information Set as follows: at least 1 IP admission or emergency department (ED) visit with a principal diagnosis of asthma; at least 4 asthma medication dispensing events; or at least 4 non-ruled-out OP office visits, IP admission, or ED visits on different days with an asthma diagnosis in any position and at least 2 asthma medication dispensing events (Supplementary Table 1, available in online article). 3 Patients with persistent asthma were then categorized by disease severity using a claims-based algorithm identifying patients with Global Initiative for Asthma step 4/5 treatment criteria (Supplementary Table 1). 5 Patients had to meet at least 1 of the following criteria for inclusion in the severe asthma cohort: at least 2 claims for medium-to high-dose ICSs and long-acting β-agonists combination, at least 2 claims for medium-to high-dose ICSs with additional controllers (eg, long-acting muscarinic antagonists or leukotriene receptor antagonists), at least 1 medical or prescription claim for a biologic therapy, or at least 180 cumulative days supply of oral corticosteroids. The index date was the date of the earliest qualifying claim for severe asthma. Patients with persistent asthma who did not meet the criteria for severe asthma were classified as having nonsevere asthma. The index date for patients with nonsevere asthma was randomly assigned based on the distribution of days from the asthma diagnosis to the index date established for patients with severe asthma. Patients were required to have 12 months of continuous database enrollment with medical and pharmacy benefits before the index date (baseline period). The follow-up period was CONCLUSIONS: Patients with SUA have significantly higher asthmarelated economic burden compared with patients with nonsevere asthma and contribute a disproportionally higher percentage of asthma-related costs.
Asthma is a heterogenous inflammatory disease characterized by variable symptoms and airflow limitation. 1 Nearly 65% of the 21 million adults in the United States with asthma have persistent (vs intermittent) asthma, which is characterized by more frequent and severe symptoms and requires longerterm medication. 1-3 Asthma presents with varying degrees of severity, ranging from mild to severe, and approximately 5% to 10% of patients with asthma have severe disease. 4 Maintenance therapies of high-dose inhaled corticosteroid (ICS) and additional controllers along with as-needed rescue medication are necessary to treat severe asthma. 5 According to the Global Initiative for Asthma, severe uncontrolled asthma (SUA) is defined as severe asthma that is difficult to treat and characterized by poor symptom control and frequent exacerbations despite ongoing treatment. 5 Asthma is a chronic condition with a continued burden on society requiring a continued need for health care utilization and time lost from work. 6 Asthma presents a significant burden on health care costs in the United States, resulting in yearly estimates of $50.3 billion in medical costs and $3 billion in losses from missed work and school days. 7 The level of health care burden is impacted by asthma severity, with severe asthma contributing to higher annual health care costs and indirect costs related to work loss than those of nonsevere asthma. 8,9 The significant economic burden of severe asthma and uncontrolled asthma has been previously reported. 8,[10][11][12][13] However, with recent developments in the treatment and management of severe asthma, especially the wider availability of biologics, updated estimates are needed to accurately assess the economic burden of SUA. The objective of this study was to describe the health care resource utilization (HCRU) and economic burden (both direct and indirect) among patients with SUA and compare it with a cohort of patients with nonsevere asthma in the United States.

DATA SOURCE
This retrospective study used US administrative claims data spanning January 1, 2013, to December 31, 2019, from the Merative MarketScan Commercial Claims and Encounters Database, the Medicare Supplemental and Coordination of Economic burden of severe uncontrolled asthma form of copayment, deductible, and coinsurance. All costs were adjusted to 2019 US dollars using the Medical Care Component of the Consumer Price index from the US Bureau of Labor Statistics. 16 Exacerbation-related health care costs among patients with SUA and severe asthma were estimated for overall exacerbations and by the type of exacerbation. Asthma exacerbations were assessed during the follow-up period and defined as including any of the following: a claim for mechanical ventilation with a corresponding same-day asthma diagnosis; any IP claim with a primary discharge diagnosis of asthma; or any ED, urgent care, or other OP visit claim with an asthma diagnosis and within 7 days of a burst of systemic corticosteroids, defined as 1 dose of injectable steroids or oral corticosteroids for at least 3 days.
Indirect costs caused by workplace absence and STD were estimated for the subset of patients whose employers provided these benefits and contributed to the HPM database. Costs associated with absenteeism used a wage constant equivalent (assigned to each individual in the study sample based upon their sex, age, and geographic region of residence) to the median hourly wage for employed (full-time, wage, and salary) workers from the US Bureau of Labor and Statistics in the latest study year (2019) to portray how additional time lost from work results in higher indirect costs (indirect cost estimates are standardized by using a wage constant). Costs associated with STD used a wage constant equivalent to 60% of the median hourly wage. The proportion of the total asthma-related direct and indirect costs attributed to severe asthma and SUA were calculated as the sum of the costs for patients with severe asthma and SUA divided by the sum of the costs of all patients with asthma.
Asthma-related direct costs assessed in the study cohort were projected for the US population. Projections are representative of patients with employer-sponsored private health insurance (ie, the types of patients include in the MarketScan Commercial and Medicare data). To project the data, person-level weights were created using the American Community Survey, conducted by the US Census Bureau, by estimating the number of people with employer-sponsored private health insurance. The person-level weights are the ratio of American Community Survey-based national estimates in the different age/sex/census division categories to the MarketScan number of persons in the same categories.

STATISTICAL ANALYSIS
Descriptive analyses were conducted to compare demographic and clinical characteristics, HCRU and costs, and indirect costs in patients with severe asthma and SUA with those with nonsevere asthma. Mean and SD were a fixed 12-month period of continuous enrollment after the index date and was used to measure study outcomes (12 months was selected to guarantee that all 4 seasons were captured for each patient, and it ensured that each patient contributed the same amount of surveillance time for the outcome measurement).
A subset of patients with severe asthma were further categorized as having SUA based on the American Thoracic Society and European Respiratory Society guidelines. 14 Patients had either at least 1 IP claim with asthma as the primary diagnosis with or without a corresponding claim for mechanical ventilation (defined using procedure codes for both invasive and noninvasive ventilation) during the stay or at least 2 ED or other OP visits with an asthma diagnosis followed by treatment with systemic corticosteroids within 7 days (1 dose of injectable steroids or oral steroids for ≥3 days).
As a final step, all patients with asthma with any nondiagnostic claims with diagnosis codes for cancer (other than basal or squamous cell skin cancer) or for any nonasthma chronic respiratory conditions, including bronchiectasis, chronic obstructive pulmonary disease, cystic fibrosis, bronchopulmonary dysplasia, sarcoidosis, lung cancer, interstitial lung disease, pulmonary hypertension, pulmonary fibrosis, or tuberculosis, in the 12-month baseline period were excluded. All code sets used to identify patients are included in Supplementary Table 2. OUTCOMES Patient demographic characteristics were reported on the index date and included age, sex, geographic region, urbanicity, health plan type, payer type (commercial or Medicare), and prescribing information. Clinical characteristics were reported during the baseline period and included the Charlson Comorbidity Index. 15 Other asthma-related comorbidities reported included allergic rhinitis, anxiety, depression, gastroesophageal reflux disease, insomnia, ischemic heart disease, nasal polyps, and chronic sinusitis. The use of biologics (ie, monoclonal antibody treatments) indicated for severe asthma, defined as having at least 2 office-administered or OP prescription claims for a biologic, was measured at any time during the follow-up period (including the index date).
HCRU and costs were measured during the 12-month follow-up period. All-cause and asthma-related HCRU and costs for IP admissions; OP visits, which include ED visits; OP pharmacy prescriptions; and total costs were estimated. Asthma-related costs were derived from medical claims with an IP or OP claim for asthma and pharmacy claims for asthma-related medications. The direct costs were the paid amounts of fully adjudicated claims, including insurer payments, as well as patient cost sharing in the  [15.7], P < 0.001) ( Table 1). Most of the patients were female (64.7% of those with severe asthma, 69.8% of those with SUA, and 68.0% of patients with nonsevere asthma) and commercially insured (88.0%, 89.7%, and 91.1% in patients with severe asthma, SUA, and nonsevere asthma, respectively). Respiratory comorbidities were more prevalent in patients with severe asthma and SUA compared with its prevalence in those with nonsevere asthma, including allergic rhinitis (29.3%, 29.6%, and 25.8%, respectively) and chronic sinusitis (10.3%, 13.3%, and 18.7%, respectively).

ALL-CAUSE AND ASTHMA-RELATED HCRU AND COSTS
All-cause and asthma-related HCRU during the 12-month follow-up period was significantly higher across all service reported for continuous variables, and statistical significance was determined using Student's t-tests. Frequencies and percentages were reported for categorical variables, and statistical significance was determined using chisquare tests. The α level of 0.05 was specified a priori as the threshold for statistical significance. Statistical analyses were performed using WPS Analytics version 4.2 (World Programming).

PATIENT CHARACTERISTICS
Of the 533,172 patients with persistent asthma eligible for analysis, 41.9% had severe asthma and 58.1% had nonsevere asthma (Figure 1). Among patients with severe asthma, 17.6% (7.4% of all eligible patients with persistent asthma) were a HEDIS criteria for persistent asthma included having at least 1 of the following: at least 1 inpatient admission or emergency department visit with an asthma diagnosis code, at least 4 asthma medication dispensing events, or at least 4 nondiagnostic claims with an asthma diagnosis and at least 2 asthma medication dispensing events. b Severe asthma criteria include at least 1 of the following (based on the Global Initiative for Asthma step 4/5 criteria): at least 2 claims for medium- to high-dose ICSs and long-acting β-agonists combination, at least 2 claims for medium- to high-dose ICSs with additional controllers (eg, long-acting muscarinic antagonists or leukotriene receptor antagonist), at least 1 medical or prescription claim for a biologic therapy, or at least 180 cumulative days supply of oral corticosteroids (within the first 12 months). c Patients with severe asthma were categorized as having uncontrolled asthma if they were hospitalized with asthma as the primary diagnosis or had at least 2 emergency department or outpatient visits with asthma diagnosis and a steroid burst within 7 days. HEDIS = Healthcare Effectiveness Data and Information Set; ICS = inhaled corticosteroid.  (Figure 2). Compared with those with nonsevere asthma, total health care costs were 31% higher in patients with SUA and 13% higher in patients with severe asthma. The mean (SD) asthma-related total health care costs during the 12-month follow-up period were also significantly higher among patients with SUA ($6,654 [$11,206]) and patients with severe asthma ($4,006 [$7,306]) compared with patients having nonsevere asthma ($1,891 [$4,536]), P < 0.001) (Figure 3). Even more pronounced, the asthma-related costs were 72% higher in patients with SUA and 53% higher among patients with severe asthma compared with the costs for those with nonsevere asthma. In addition, asthma-related costs represented a higher proportion of all-cause costs in patients with SUA (28%) and severe asthma (22%) compared with the costs for patients with nonsevere asthma (12%). types (IP, ED, office visits, laboratory, radiology, and other OP services) in patients with SUA compared with those with nonsevere asthma (all P < 0.001). A larger proportion of patients with SUA compared with those with nonsevere asthma had an IP admission (16.0% vs 10.6% all-cause; 6.3% vs 0.7% asthma related) or an ED visit (42.8% vs 37.7% all-cause; 26.2% vs 19.3% asthma related). The use of OP services (office visits, laboratory, radiology, and other services) and pharmacy prescriptions was consistently higher with increasing disease burden (nonsevere to severe to SUA). The largest differences (all P < 0.001) were in the mean (SD) number of asthma-related office visits (SUA, 4 Table 4).

PROPORTION OF TOTAL ASTHMA-RELATED COSTS DUE TO SUA AND SEVERE ASTHMA
Although patients with severe asthma made up 41.9% of the total persistent asthma study population, they contributed disproportionately higher costs (60.5%) to the total asthma-related direct costs (Table 2), with the effect more evident among patients with SUA (7.4% of study population Among the 39,380 patients with SUA, the mean (SD) number of exacerbations were 2.5 (1.2), incurring mean (SD) direct costs of $2,440 ($8,031), which was higher when compared with those of severe asthma (mean [SD] exacerbations: 1.6 [1.1], incurring $1,349 [$5,874] direct costs). The majority of both patients with SUA and patients with severe asthma with an exacerbation reported at least 1 event in the OP setting (92.5% and 91.7%, respectively); however, a larger proportion of patients with SUA (vs severe asthma) had an exacerbation in the IP (6.2% vs 2.6%) or ED (21.1% vs 13.9%) settings. Exacerbations requiring mechanical ventilation accounted for the highest mean (SD) cost burden in both patients with SUA ($46,765 [$61,319]) and patients with severe asthma ($41,735 [$57,153]) but were very rare. Only 0.1% (n = 184) of patients with severe asthma and 0.2% (n = 87) of patients with SUA had an exacerbation that required mechanical ventilation.

INDIRECT COSTS FROM PRODUCTIVITY LOSS
For the subset of patients with asthma with workplace absenteeism eligibility (absence n = 11,049 and STD n = 73,973), a P < 0.001 vs nonsevere asthma. b Outpatient service includes emergency department visits, outpatient office visits, laboratory services, radiology services, and other outpatient services. SUA = severe uncontrolled asthma.

FIGURE 2
All-Cause Costs During the 12-Month Follow-Up Period Economic burden of severe uncontrolled asthma contributed 17.7% of total asthma-related costs). Patients with SUA also contributed disproportionately high indirect costs due to STD compared with those with nonsevere asthma, although this was less pronounced than with the direct costs. Patients with SUA made up 7.5% of the STDeligible cohort but contributed 11.4% of related indirect costs. For work absence, patients with SUA made up 6.8% of the absence-eligible cohort but contributed 7.5% of the related indirect costs ( Table 2). The national estimates of patients with asthma with employer-sponsored health insurance in the United States were 240,190 with SUA, 1,381,155 with severe asthma and 3,383,311 with nonsevere asthma. The national estimates indicated that those with severe asthma accounted for 59.1% of the asthma-related HCRU cost burden despite making up only 40.8% of patients with persistent asthma (Supplemental Figure 1). This disproportionate contribution was markedly evident among patients with SUA, where 7.1% of patients contribute 17.1% of the total asthma-related HCRU cost burden.

Discussion
This retrospective real-world analysis demonstrated the extent to which, during a 12-month observational period, patients with SUA had significantly higher HCRU and costs (both all-cause and asthma-related) compared with patients with nonsevere asthma. Patients with SUA (vs nonsevere) had a significantly larger proportion with IP admissions and ED visits and a higher number of asthma-related office visits and pharmacy prescriptions. Patients with SUA had a higher number of asthma exacerbations (mean [ Patients with SUA also incurred higher indirect costs and were significantly more likely to take time off work compared with those with nonsevere asthma.
Overall, 7.4% of this study population met the definition of SUA, 14 which is slightly higher but generally consistent a P < 0.001 vs nonsevere asthma. b Outpatient service includes emergency department visits, outpatient office visits, laboratory services, radiology services, and other outpatient services. SUA = severe uncontrolled asthma.

FIGURE 3
Asthma-Related Costs During the 12-Month Follow-Up Period asthma. Indirect costs were higher for those with severe asthma vs nonsevere for absence-related costs ($7,227 vs $6,956, P = 0.007) and STD-related costs ($6,332 vs $5,679, P = 004), with costs driven mostly by patients with SUA ($7,219 for absenteeism-related costs and $6,601 for STD-related costs). 10 The current analysis augments prior work with more recent data and found that economic burden (both direct and indirect) increases with disease severity from nonsevere to severe to SUA. These current data are important, as they provide accurate cost estimates as newer treatment options targeted for SUA are increasing.

LIMITATIONS
This study had several limitations. The data were collected for administrative purposes and are subject to data entry and coding errors, which may result in misclassification when categorizing patients by asthma status (persistent, severe, or uncontrolled). It is also assumed that patients take the medications purchased as prescribed (ie, that they are compliant or adherent to treatment), which cannot be confirmed with claims data and could lead to a misinterpretation of the results. Additionally, the reason for work loss claims was not captured in the database, and the claims cannot be specifically linked to asthma. It is possible that work loss by absenteeism, STD, or both may not have been a consequence of asthma but rather because of other comorbid diseases. However, one would expect the differences in absenteeism and STD between the cohorts to largely be attributable to differences in asthma severity and control. As administrative claims data lack the clinical detail needed to adequately control for differences in patients' characteristics, this study did not use matching or multivariate analyses. This decision the MarketScan database using data through December 31, 2015, reported findings consistent with the current analysis. 10 Among patients with asthma aged 12 years and older, it was found that direct all-cause health care costs were 21% greater among patients with severe asthma vs those with nonsevere asthma (multivariable adjusted cost ratio, 1.21; 95% CI = 1.20 -1.22), with the patients with SUA incurring even greater costs. Asthma-related costs were more than twice as high in patients with severe asthma compared with those with nonsevere asthma (multivariable adjusted cost ratio, 2.20; 95% CI = 2.19 -2.22), with patients with SUA incurring even greater costs. The study also found that a higher proportion of patients with severe asthma and SUA experienced work loss and longer periods of missed work because of absence and STD than did patients with nonsevere with the rates reported in Hankin et al, published in 2013, reporting 3% to 5% with severe uncontrolled disease. 17 SUA has been associated with increased HCRU (IP admissions and ED visits) and costs as well as lost productivity from missed work. [10][11][12] The findings of this study augment prior literature with updated data reporting the significant economic burden that SUA contributes to health care costs and work productivity loss. 12 This study also adds data documenting that although patients with SUA represent a small proportion of patients with persistent asthma, they contribute a disproportionate percentage of asthma related costs (~7% of patients contributing ~17% of costs) providing further evidence for the need of therapies to successfully manage disease.
A previous study of the direct and indirect costs of severe asthma in indirect costs compared with those with nonsevere asthma. The estimated asthma-related direct costs from this study population were consistent with the projections of US national estimates, with patients with severe asthma and SUA contributing disproportionally higher costs than those with nonsevere asthma.

DISCLOSURES
This study was funded by Amgen and AstraZeneca. The design and analysis for this study was conducted primarily by Merative. Amgen and AstraZeneca provided funding to support protocol development, data analysis, and manuscript development activities associated with this study. Dr Burnette is on the advisory board and a consultant for GSK, a consultant and member of the advisory boards and speakers' bureaus of Sanofi, Genzyme, Regeneron, AstraZeneca, and Amgen Inc. Dr Wang, Dr Rane, Dr Lindsley, and Dr Llanos are employees and shareholders of Amgen Inc. Dr Chung and Dr Ambrose are employees and shareholders of AstraZeneca. Ms Princic and Ms Park are employees of Merative, which received funding from Amgen to conduct this study.
was supported by the finding that the observed differences between the demographic and clinical characteristics measured in our study were not clinically meaningful. Although this is a limitation of the analysis, the magnitude of differences observed between patients with SUA and patients with nonsevere asthma was large and unlikely to be notably changed by any adjustment. The observed, unadjusted results also more accurately describe the real-world populations, which was a primary focus of the current analysis. Finally, the projected direct costs for SUA ($5.7 billion) in our study were lower than those estimated in a study estimating the economic burden of uncontrolled asthma in the United States ($14.6 billion for uncontrolled asthma in 2019). 11 The differences were likely because the estimates in our study are based on patients with employer-sponsored insurance (as this study used data from patients with commercial or Medicare supplemental insurance; thus, findings and projections may not be generalizable to patients with other types of insurance or without insurance), whereas the previous study determined estimates for the entire uncontrolled population in the United States. Differences across the 2 studies in the definition of uncontrolled asthma and the study populations (adult patients in this study vs adolescents and adults in the previous) could also have contributed to the differences in estimates.

Conclusions
Patients with severe asthma had significantly higher all-cause and asthma-related health care costs compared with patients with nonsevere asthma, and those with SUA experienced the highest economic burden. Patients with SUA were also significantly more likely to require time off from work and incur higher